TGFR1_HUMAN
Source:
PM23856902
Marked as 'Integral membrane protein'
Confidence:
low (only semi-automatic identification from reviews)
Search PubMed for
(RBC AND this entry)
Gene names:
TGFBR1
, ALK5, SKR4
Protein names and data:
TGFR1_HUMAN
, TGF-beta receptor type-1; TGFR-1; 2.7.11.30
, Activin A receptor type II-like protein kinase of 53kD; Activin receptor-like kinase 5; ALK-5; ALK5; Serine/threonine-protein kinase receptor R4; SKR4; TGF-beta type I receptor; Transforming growth factor-beta receptor type I; TGF-beta receptor type I; TbetaR-I; Flags: Precursor
Lenght: 503 a.a.
Mass: 55960 Da
fasta formatted sequence
Function:
Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non- canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.
Catalytic activity:
ATP + [receptor-protein] = ADP + [receptor- protein] phosphate.
Disease:
( OMIM:
132800
190181
608967
609192
)
Loeys-Dietz syndrome 1A (LDS1A) [MIM:609192]: An aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree. Note=The disease is caused by mutations affecting the gene represented in this entry. Loeys-Dietz syndrome 2A (LDS2A) [MIM:608967]: An aortic aneurysm syndrome with widespread systemic involvement. Physical findings include diffuse arterial aneurysms and dissections, prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. Loeys-Dietz syndrome type 2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients. Note=The disease is caused by mutations affecting the gene represented in this entry. TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:16791849). This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS2A by having aneurysms restricted to thoracic aorta. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS2A by the OMIM resource. Multiple self-healing squamous epithelioma (MSSE) [MIM:132800]: A disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars. Note=The disease is caused by mutations affecting the gene represented in this entry.
Cellular location:
Cell membrane; Single-pass type I membrane protein. Cell junction, tight junction.
Tissue specificity:
Found in all tissues examined, most abundant in placenta and least abundant in brain and heart.
Genetic variants
24 - 26
Missing (in allele TGFBR1*6A; could be a tumor susceptibility allele). VAR_022342
26 - 26
A -> AA (in allele TGFBR1*10A; rare polymorphism). VAR_022343
41 - 41
C -> Y (in MSSE; hypomorphic mutation). VAR_065826
45 - 45
N -> S (in MSSE; hypomorphic mutation). VAR_065827
52 - 52
G -> R (in MSSE; hypomorphic mutation). VAR_065828
83 - 83
P -> L (in MSSE; hypomorphic mutation). VAR_065829
139 - 139
I -> V. VAR_054160
153 - 153
V -> I (in dbSNP:rs56014374). VAR_041412
56014374
200 - 200
T -> I (in LDS1A). VAR_022344
232 - 232
K -> E (in LDS2A). VAR_029481
241 - 241
S -> L (in LDS1A). VAR_029482
266 - 266
D -> Y (in LDS1A). VAR_066720
267 - 267
N -> H (in a patient with Marfan syndrome). VAR_029483
291 - 291
Y -> C (in dbSNP:rs35974499). VAR_041413
35974499
318 - 318
M -> R (in LDS1A). VAR_022345
351 - 351
D -> G (in LDS1A). VAR_066721
375 - 375
T -> I (in LDS1A). VAR_066722
400 - 400
D -> G (in LDS1A). VAR_022346
487 - 487
R -> P (in LDS1A and LDS2A). VAR_022347
487 - 487
R -> Q (in LDS1A and LDS2A). VAR_029484
487 - 487
R -> W (in LDS2A). VAR_029485
Database cross-references
UniProt:
P36897
Ensembl:
ENST00000374990
Ensembl:
ENST00000374994
Ensembl:
ENST00000552516
MIM:
132800
MIM:
190181
MIM:
608967
MIM:
609192
neXtProt:
NX_P36897
Antibodypedia:
P36897
(may not find the protein thus also not any antibody)
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